OTK18, a zinc-finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions
OTK18, a zinc-finger protein, regulates human immunodeficiency virus type 1 long terminal repeat through two distinct regulatory regions
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DOI：
10.1099/vir.0.82066-0
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发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Ikezu, Tsuneya
中科院分区：
文献类型：
--
作者：
Horiba, Masahide;Martinez, Lindsey B.;Ikezu, Tsuneya
我们的实验室先前已经证明，OTK18是一种人类免疫缺陷病毒（HIV）诱导的锌指蛋白，可以减少感染的人巨噬细胞中子代病毒粒子的产生。OTK18抗病毒活性是通过抑制tat诱导的HIV-1长末端重复序列（LTR）启动子活性介导的。通过使用LTR扫描突变载体，确定了负责otk18介导的LTR抑制的特定区域。通过增强型dna转录因子ELISA系统鉴定出两个不同的LTR区域是潜在的otk18结合位点；LTR中负调控元件（NRE）位于-255/-238，ets结合位点（EBS）位于-150/-139。此外，LTR中EBS的缺失阻断了otk18介导的LTR抑制。这些数据表明OTK18通过两个不同的调控元件抑制LTR活性。这些区域的自发突变可能使HIV-1逃避OTK18在人巨噬细胞中的抗逆转录病毒活性。
It has previously been shown by our laboratory that OTK18, a human immunodeficiency virus (HIV)inducible zinc-finger protein, reduces progeny-virion production in infected human macrophages. OTK18 antiviral activity is mediated through suppression of Tat-induced HIV-1 long terminal repeat (LTR) promoter activity. Through the use of LTR-scanning mutant vectors, the specific regions responsible for OTK18-mediated LTR suppression have been defined. Two different LTR regions were identified as potential OTK18-binding sites by an enhanced DNA-transcription factor ELISA system; the negative-regulatory element (NRE) at -255/-238 and the Ets-binding site (EBS) at -150/-139 in the LTR. In addition, deletion of the EBS in the LTR blocked OTK18-mediated LTR suppression. These data indicate that OTK18 suppresses LTR activity through two distinct regulatory elements. Spontaneous mutations in these regions might enable HIV-1 to escape from OTK18 antiretroviral activity in human macrophages.